Medicine traditionally utilizes pharmacologic agents or surgical interventions for the treatment of disease. Specific targeting or localization of pharmacologic or biologic agents to desired organs and tissues is a complex challenge.
For example, delivery of agents to tumors to treat or cure cancer is limited by non-specific targeting, agent degradation, and high systemic toxicity, to name a few. Treatments of conditions such as cancer remain relatively ineffective as evidenced by high rates of cancer recurrence and low survival; cancer is a leading cause of death for both men and women in the United States (Jemal et al., CA Cancer J. Clin., 60:277-300, 2010). Current methods of cancer treatment include chemotherapy, radiation treatment, and surgical resection.
Other medical applications which utilize drug delivery technologies include immunological applications, pain control, wound healing, infectious disease, transplants, and the development of vaccines. Potential drug candidates often present solubility, toxicity, and/or pharmacokinetic concerns. Thus, there is a broad need for locally and regionally targeted and sustained delivery of therapeutic agents.
Certain polyesters, polycarbonates, and polyamides are biodegradable polymers with low toxicity and degradation properties. Such polymers include poly(ε-caprolactone), poly(p-dioxanone), poly(trimethylene carbonate), and most notably poly(glycolic acid) and poly(lactic acid)(see, e.g., Agrawal et al., Biomaterials, 13:176-182, 1992; Attawia et al., J. Biomed. Mater. Res., 29:1233-140, 1995; Heller et al., Adv. Drug Deliv. Rev., 54:1015-1039, 2002; Miller and Williams, Biomaterials, 8:129-137, 1987; and Athanasiou et al., Arthroscopy, 14:726-737, 1998). These polymers are used in a variety of applications including the delivery of therapeutic agents. However, physical properties of the aforementioned polymers are limited by monomer selection, polymerization techniques and post-polymerization modifications. Properties of interest include thermal transition temperatures, bulk strength, flexibility or elasticity, degradation, crystallinity, and hydrophobicity. When polymers are utilized for in vivo applications, the physical properties of the material affect host response.
Hence, a need exists for polymers and delivery systems with desired characteristics that are effective for treatment of diseases and conditions in vivo and that can be tailored for specific therapeutic needs and tissue characteristics.